Search for: [Abstract = "ular interactions as the previously described compound C17. Results of molecular dynamics simulation revealed that the compound can keep stable conformation within the CBR1 catalytic site in the whole range of simulation time \(20 ns\), suggesting that ASP9521 may be a CBR1 ligand. This hypothesis was confirmed in inhibitory enzymatic assay \(IC50 = 44,00 μM\). Additionally, ASP9521 ameliorated anticancer activity of daunorubicin against pulmonary cancer cells \(cell line A549\), decreasing by 14,25% drug concentration necessary to inhibit cells growth by a half. Identification of a moderate dual CBR1\-AKR1C3 inhibitory activity of ASP9521 led to initiation of searching for new chemotypes of dual inhibitors of main ANT reductases, the combined effect of which may surpass the use of a selective inhibitor. For this purpose, selected CBR1 and AKR1C3 crystal structures were optimized, using computer tools and methods described in the first part of the research. 36 potential CBR1\-AKR1C3 inhibitors were selected after prospective virtual screening performed on the best rated models \(11E3 and 74H1\). Most of the compounds turned out to be moderate or potent AKR1C3 inhibitors \(the most potent inhibitor was compound P27, with IC50 AKR1C3 = 2,25 μM\), with moderate or weak CBR1 inhibition. Additional analysis of compounds previously pointed as CBR1 inhibitors revealed"]

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